Citalopram in Treating Postmenopausal Women With Hot Flashes

OBJECTIVES:

Primary

- Evaluate the efficacy of three different doses of citalopram hydrobromide on hot flash
scores in postmenopausal women with a history of breast cancer or in postmenopausal
women who do not wish to take estrogen replacement therapy for fear of increased risk
of breast cancer.

Secondary

- Compare the side effect profile of these regimens in these patients.

- Compare the effects of these regimens on the secondary outcome of mood and interference
with activities from hot flashes.

- Determine if CYP2C19 and CYP2D6 polymorphisms predict efficacy of various doses of
citalopram hydrobromide.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to age (18-49 years vs ≥ 50 years), tamoxifen (yes vs no),
selective estrogen-receptor modulators (SERMs) (yes vs no), aromatase inhibitors (yes vs
no), duration of hot flashes (< 9 months vs ≥ 9 months), and frequency of hot flashes per
day (< 4 vs 4-9 vs ≥ 10). Patients are randomized to 1 of 4 treatment arms.

- Arm I (low-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram
once daily in weeks 2-7.

- Arm II (medium-dose citalopram hydrobromide): Patients receive 1 tablet of oral
citalopram once daily in week 2 and 2 tablets once daily in weeks 3-7.

- Arm III (high-dose citalopram hydrobromide): Patients receive 1 tablet of oral
citalopram once daily in week 2, 2 tablets once daily in week 3, and 3 tablets once
daily in weeks 4-7.

- Arm IV (placebo): Patients receive 1-3 placebo tablets once daily in weeks 2-7. All
patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood
collection periodically during study treatment for translational research studies.

A Symptom Experience diary is completed weekly and Profile of Mood States and Hot
Flash-Related Interference Scale questionnaires are completed at baseline and in week 7.

DISEASE CHARACTERISTICS:

- Must meet 1 of the following criteria:

- History of breast cancer

- No current malignant disease

- No history of breast cancer and refused estrogen replacement therapy due to
perceived increased risk of breast cancer

- Bothersome hot flashes, defined as hot flashes ≥ 14 times/week and of sufficient
severity to make the patient desire therapeutic intervention

- Presence of hot flashes ≥ 1 month prior to study entry

- Hormone receptor status not specified

PATIENT CHARACTERISTICS:

- Female

- Postmenopausal, as defined by 1 of the following criteria:

- Absence of a menstrual period in the past 12 months

- Bilateral oophorectomy

- Absence of a menstrual period in the past 6 months with follicle-stimulating
hormone (FSH) level > 40 mIU/mL

- ECOG performance status 0-1

- Life expectancy ≥ 6 months

- Willing to provide blood samples during study participation

- No history of allergic or other adverse reactions to citalopram hydrobromide or other
selective serotonin reuptake inhibitors (SSRIs)

- No documented mania or hypomania

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since prior and no concurrent antineoplastic chemotherapy

- At least 4 weeks since prior and no concurrent androgens, estrogens, or
progestational agents

- At least 3 months since prior antidepressant use, including Hypericum perforatum (St.
John's wort)

- Concurrent tamoxifen, raloxifene, or aromatase inhibitors allowed if on a constant
dose for ≥ 4 weeks and continuing medication during study period

- No other concurrent or planned agents for treating hot flashes (e.g., phenobarbital,
megestrol, or clonidine)

- Stable dose of vitamin E allowed as long as it was started > 30 days prior to
study entry

- Concurrent soy allowed

- Concurrent gabapentin allowed for reasons other than hot flashes if on a constant
dose for ≥ 1 month and continuing during study period